Nobel for Test-Tube Evolution Controlling Protein Evolution in the Lab Has Led to Greener Technologies and New Medicines

NEWS IN FOCUS

CHEMISTRY Nobel for test-tube evolution Controlling protein evolution in the lab has led to greener technologies and new medicines.

BY ELIZABETH GIBNEY, RICHARD VAN breeding a racehorse,” she says. was launched, says co-founder David Chiswell, NOORDEN, HEIDI LEDFORD, DAVIDE In 1985, Smith pioneered a technique that and it struggled to find investors. “Nobody CASTELVECCHI & MATTHEW WARREN uses a bacteriophage — a virus that infects in the world believed that antibodies were bacteria — as a host that displays a protein really good,” says Chiswell, who is now chief ays to speed up and control the on its outer coat, allowing researchers to find executive of Kymab, an antibody company in evolution of proteins to produce other molecules that interact with the protein. Cambridge. greener technologies and new Winter developed and improved this technol- Arnold also faced a battle when she put Wmedicines have won three scientists the 2018 ogy, called phage display, and invented ways forward the idea of evolving proteins in the lab, Nobel Prize in Chemistry. to use it to evolve antibodies adapted for use as says Dane Wittrup, a protein engineer at the Chemical engineer Frances Massachusetts Institute of Tech- Arnold, at the California Insti- nology in Cambridge. Research- tute of Technology in Pasadena, ers thought then that they would is just the second woman to be able to sit down at a computer have won the prize in the past 50 and rationally design proteins to years. She was awarded half of the carry out specific functions. “But 9-million-Swedish-krona (US$1- now, by and large, directed evolu- million) pot. The remaining half tion is how the work is done.” was shared between Gregory Winter says that a woman with Winter at the MRC Laboratory of cancer who had received an early, Molecular Biology in Cambridge, experimental version of one of his UK, and George Smith at the Uni- humanized antibodies against a versity of Missouri in Columbia. cancer-related protein drove him Arnold carried out pioneer- to push his research out of the lab- ing work in the 1990s on the oratory and into the clinic. When MISSOURI-COLUMBIA UNIV. MACHAJ;L–R: AGA CALTECH; ‘directed evolution’ of enzymes Nobel laureates Gregory Winter (left), Frances Arnold and George Smith. Winter warned her that the effects — proteins that catalyse chemical of the therapy might not last, she reactions. She devised a method for inducing therapeutics. Today, antibodies evolved using told him she only needed to live for a few more mutations in enzyme-producing bacteria and this method can neutralize toxins and coun- months, so that she could help her dying hus- then screening and selecting the bacteria to teract autoimmune diseases. band. “I was so choked by that,” Winter says. speed up and direct enzyme evolution. These The first humanized antibody, called Before Arnold, the last woman to win the enzymes are now used in the production of adalimumab (Humira), was discovered Nobel Prize in Chemistry was Ada Yonath, a biofuels and drugs. by Cambridge Antibody Technology — a crystallographer at the Weizmann Institute of “Biology has this one process that’s respon- company that Winter co-founded in 1989 — Science in Rehovot, Israel, who won in 2009 for sible for all this glorious complexity we see in and was approved for treating rheumatoid mapping the structure of the ribosome, which nature,” she told Nature shortly after the prize arthritis in 2002. It is also used to treat psoriasis generates proteins from the genetic code in announcement on 3 October. But whereas and inflammatory bowel diseases. In 2017, it cells. Before her, the most recent woman to nature operates blindly, Arnold’s techniques was the world’s top-selling drug, generating win was crystallographer Dorothy Hodgkin, accelerate natural selection towards produc- revenues of $18.4 billion. in 1964. Arnold is just the fifth female winner ing enzymes with known properties. “It’s like Scepticism abounded when the company in the prize’s history. ■

EUROPE

Tiny space fleet could track CO2 Project could help to show whether nations are meeting pledges to cut emissions.

BY ALEXANDRA WITZE track daily fluctuations in greenhouse-gas might also come online in the late 2020s. emissions. Several satellites currently monitor CO2 uropean researchers are developing a Developers with the 3-year, €3-million emissions, including Japan’s GOSAT, the miniaturized instrument that could pre- (US$3.5-million) project envisage it comple- United States’s Orbiting Carbon Observa- cisely measure carbon dioxide coming menting more-expansive efforts to monitor tory-2 (OCO-2) and China’s TanSat. But none Efrom cities and power plants. If it works, the CO2 from space, such as a proposed set of new of them launched with the explicit goal of device could fly aboard a constellation of small Sentinel Earth-observing satellites from the tracking compliance with global treaties. satellites starting in the late 2020s, helping to European Space Agency. If approved, those In 2015, before the signing of the Paris

IN FOCUS NEWS

accord to limit greenhouse-gas emissions, the globe once a week, and could fly over particu- concept for miniaturized sensors, but using a European Commission began exploring how lar areas of interest once a day. Together, they different type of spectrometer. it could develop satellites to assess whether could monitor frequent changes in carbon SCARBO scientists plan to test their nations are abiding by their climate pledges. emissions, such as morning and afternoon instrument aboard a research aeroplane in The new, small sensor could play a part in surges from an industrial area. 2020. It will fly alongside a Dutch-built instru- that. “We want to improve the accuracy of But first, SCARBO scientists have to show that ment to study atmospheric aerosols, which are monitoring anthropogenic CO2 emissions,” their plan can work. At its heart is a miniaturized a major source of error when trying to measure says Laure Brooker Lizon-Tati, an engineer spectrometer — no longer than an outstretched greenhouse gases. The test will be the first time with Airbus Defence and Space in Toulouse, hand — that would that aerosols and CO2 are measured simultane- France. She coordinates the project, called the “We want to detect CO2 concentra- ously to improve the quality of data on green- Space Carbon Observatory (SCARBO), which improve the tions in the air below. house-gas emissions, says Lizon-Tati. is being developed by a consortium of eight accuracy of Fitting a spectrom- SCARBO is focusing on CO2 monitoring, European companies and research institutions. monitoring eter onto a small satel- although it would also be useful for tracking Team scientists were scheduled to describe anthropogenic lite requires shrinking methane emissions, says Le Coarer. Several the first results at a space-optics conference CO2 emissions.” optics and develop- private efforts to monitor methane emissions this week in Chania, Greece. ing new methods for cheaply from space are already under way, The proposed Sentinel satellites would analysing CO2 concentrations. “It’s a real chal- including a Canadian microsatellite that has precisely measure greenhouse gases around lenge,” says Bovensmann. been flying since 2016 and a planned small sat- the world. But they would not be able to make The scientists’ goal is to measure CO2 ellite from the Environmental Defense Fund, daily measurements above places of interest, concentrations to an accuracy of less than 1 part an advocacy group in New York City. ■ such as cities. “This is where a constellation per million at a resolution of 2 kilometres — of tiny SCARBO systems could come into the comparable to the data collected by larger sat- game,” says Heinrich Bovensmann, a remote- ellites now in orbit. CORRECTION sensing researcher at the University of Bremen “We want to prove the technology can The News story ‘Peru plans oil clean-up’ in Germany. achieve these types of measurements,” says (Nature 562, 18–19; 2018) erroneously Etienne Le Coarer of the University Grenoble- stated that the United Nations Development SMALL STEPS Alpes in France, which is building the instru- Programme (UNDP) funded a study on SCARBO satellites would weigh just ment along with the ONERA French aerospace remediation strategies. In fact, the Peruvian 50 kilograms each, roughly one-tenth the mass laboratory in Palaiseau. government funded the study and the of OCO-2 or TanSat. An estimated two dozen NASA’s Jet Propulsion Laboratory in UNDP conducted it. working together would be able to cover the Pasadena, California, has worked on a similar